Inhibition of dendritic cell maturation and function is independent of heme oxygenase 1 but requires the activation of STAT3.

Abstract

The induction of heme oxygenase 1 (HO-1) by a single treatment with cobalt protoporphyrin (CoPPIX) protects against inflammatory liver failure and ischemia reperfusion injury after allotransplantation. In this context, the HO-1-mediated inhibition of donor-derived dendritic cell maturation and migration is discussed as one of the key events of graft protection. To investigate the poorly understood mechanism of CoPPIX-induced HO-1 activity in more detail, we performed gene expression analysis in murine liver, revealing the up-regulation of STAT3 after CoPPIX treatment. By using wild-type and HO-1-deficient dendritic cells we demonstrated that LPS-induced maturation is dependent on STAT3 phosphorylation and independent of HO-1 activity. In summary, our observations revise our understanding of the anti-inflammatory properties of HO-1 and highlight the immunomodulatory capacity of STAT3, which might be of further interest for targeting undesired immune responses, including ischemia reperfusion injury.

• Authors: Mir-Farzin Mashreghi, Roman Klemz, Isabela Schmitt Knosalla, Bernhard Gerstmayer, Uwe Janssen, Roland Buelow, Alicja Jozkowicz, Jozef Dulak, Hans-Dieter Volk, Katja Kotsch
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 180 Issue 12 Pg. 7919-30 (Jun 15 2008) ISSN: 0022-1767 [Print] United States
• PMID: 18523255 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Growth Inhibitors
• Lipopolysaccharides
• Protoporphyrins
• STAT3 Transcription Factor
• Stat3 protein, mouse
• cobaltiprotoporphyrin
• Heme Oxygenase-1

Topics

• Animals
• Bone Marrow Cells (enzymology)
• Cell Differentiation (drug effects, immunology)
• Cells, Cultured
• Coculture Techniques
• Dendritic Cells (cytology, enzymology, immunology, metabolism)
• Gene Expression Profiling
• Growth Inhibitors (administration & dosage, physiology)
• Heme Oxygenase-1 (biosynthesis, deficiency, genetics, physiology)
• Lipopolysaccharides (antagonists & inhibitors, pharmacology)
• MAP Kinase Signaling System (drug effects, genetics, immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Oligonucleotide Array Sequence Analysis
• Phosphorylation
• Protoporphyrins (administration & dosage, pharmacology)
• STAT3 Transcription Factor (biosynthesis, metabolism, physiology)